Long-term outcomes with emicizumab in hemophilia A without inhibitors: results from the HAVEN 3 and 4 studies

Johnny Mahlangu; Víctor Jiménez-Yuste; Giuliana Ventriglia; Markus Niggli; Simona Barlera; Cédric Hermans; Michaela Lehle; Pratima Chowdary; Lyle Jew; Jerzy Windyga; Laurent Frenzel; Christophe Schmitt; Giancarlo Castaman; Steven W Pipe

doi:10.1016/j.rpth.2024.102364

Long-term outcomes with emicizumab in hemophilia A without inhibitors: results from the HAVEN 3 and 4 studies

Res Pract Thromb Haemost. 2024 Mar 1;8(2):102364. doi: 10.1016/j.rpth.2024.102364. eCollection 2024 Feb.

Authors

Affiliations

¹ Faculty of Health Sciences, University of the Witwatersrand, National Health Laboratory Service, Johannesburg, South Africa.
² Jefe de Servicio de Hematología, La Paz University Hospital-IdiPaz, Autónoma University, Madrid, Spain.
³ Oncology and Hematology Product Development, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
⁴ Product Development Data Sciences, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
⁵ Department of Biometrics, Parexel International, Milan, Italy.
⁶ Haemostasis and Thrombosis Unit, Division of Haematology, Cliniques Universitaires Saint-Luc, Catholic University of Louvain, Brussels, Belgium.
⁷ Katharine Dormandy Haemophilia and Thrombosis Unit, Royal Free London, London, United Kingdom.
⁸ Product Development Safety, Genentech, Inc. South San Francisco, California, USA.
⁹ Department of Hemostasis Disorders and Internal Medicine, Laboratory of Hemostasis and Metabolic Diseases, Institute of Hematology and Transfusion Medicine, Warsaw, Poland.
¹⁰ Department of Hematology, Necker-Enfants Malades Hospital, Paris, France.
¹¹ Department of Clinical Pharmacology, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
¹² Center for Bleeding Disorders and Coagulation, Careggi University Hospital, Florence, Italy.
¹³ Departments of Pediatrics and Pathology, University of Michigan, Ann Arbor, Michigan, USA.

Abstract

Background: Emicizumab, a bispecific monoclonal antibody, bridges activated factor (F) IX and FX, mimicking the function of missing or deficient activated FVIII in people with hemophilia A (HA).

Objectives: To evaluate the long-term efficacy and safety of emicizumab prophylaxis in people with HA without FVIII inhibitors in the HAVEN 3 and 4 studies.

Methods: HAVEN 3 and 4 were phase 3 open-label studies. Participants received emicizumab maintenance doses of 1.5 mg/kg every week or 3 mg/kg every 2 weeks (HAVEN 3), or 6 mg/kg every 4 weeks (HAVEN 4). Long-term efficacy and safety were assessed.

Results: A total of 151 and 40 individuals without FVIII inhibitors received emicizumab in HAVEN 3 and 4, respectively. At the last patient, last visit dates (May 12, 2022 [HAVEN 3] and June 29, 2022 [HAVEN 4]), the median (range) duration of emicizumab exposure across the 2 studies was 248.1 (6.1-287.1) weeks. The mean (95% CI) annualized bleed rate for treated bleeds was 2.0 (0.23-7.15) for weeks 1 to 24, decreasing to 0.9 (0.01-5.28) by weeks 217 to 240. Overall, 188 (98.4%) participants experienced ≥1 adverse event (AE), with 185 treatment-related AEs in 71 (37.2%) participants. Forty-four (23.0%) participants reported a serious AE. Two thromboembolic events were reported, which were deemed unrelated to emicizumab by the investigator. No thrombotic microangiopathies were reported.

Conclusion: With nearly 5 years of emicizumab exposure across the HAVEN 3 and 4 studies in people with HA without inhibitors, these data indicate continued bleed control with no new safety signals observed during long-term follow-up.

Keywords: efficacy; emicizumab; hemophilia A; prophylaxis; safety.